Lutetium after second-line hormonal treatment [PBP-301] [SPLASH]

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Point Biopharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Jan 2022 → ongoing

Decision date (initial)

2024-11-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Point Biopharma Inc.

External identifiers

EU CT number

2024-515604-39-00

EudraCT number

2021-002641-15

WHO UTN

U1111-1311-5970

ClinicalTrials.gov

NCT04647526

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacokinetic

To determine the efficacy of 177Lu-PNT2002 versus abiraterone or enzalutamide in delaying radiographic progression in patients with mCRPC who have progressed on ARAT.

Secondary objectives 5

1. 1. To assess the radiographic response to 177Lu-PNT2002 versus abiraterone or enzalutamide.
2. 2. To determine the effect of 177Lu-PNT2002 versus abiraterone or enzalutamide on overall survival (OS) in patients who have progressed on ARAT.
3. 3. To determine the effect of 177Lu-PNT2002 versus abiraterone or enzalutamide on developing a symptomatic skeletal-related event.
4. 4. To determine the effect of 177Lu-PNT2002 versus abiraterone or enzalutamide on prostate-specific antigen (PSA) kinetics in patients who have progressed on ARAT.
5. 5. Safety Objective: To evaluate the safety and tolerability of 177Lu-PNT2002 versus abiraterone or enzalutamide.

Conditions and MedDRA coding

Metastatic castration-resistant prostate cancer (mCRPC)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Male aged 18 years or older.
2. 2. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
3. 3. Ineligible or averse to chemotherapeutic treatment options.
4. 4. Patients must have progressive mCRPC at the time of consent based on at least 1 of the following criteria: a. Serum/plasma PSA progression defined as increase in PSA greater than 25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart. b. Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of 1 or a new lesion. c. Progression of bone disease defined as the appearance of two or more new lesions by bone scan.
5. 5. Progression on previous treatment with one ARAT (abiraterone or enzalutamide or darolutamide or apalutamide) in either the CSPC or CRPC setting.
6. 6. PSMA-PET scan (i.e., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by the sponsor's central reader.
7. 7. Castrate circulating testosterone levels (<1.7 nmol/L or <50 ng/dL).
8. 8. Adequate organ function, independent of transfusion: a. Bone marrow reserve: i. White blood cell count ≥2.5 × 109/L OR ANC≥1.5 × 109/L. ii. Platelets ≥100 × 109/L. iii. Hemoglobin ≥8 g/dL. b. Liver function: i. Total bilirubin ≤1.5 × institutional upper limit of normal (ULN). For patients with known Gilbert’s syndrome, ≤3 × ULN is permitted. ii. Alanine aminotransferase and aspartate aminotransferase ≤3.0 × ULN. c. Renal function: i. Serum/plasma creatinine ≤1.5 × ULN or CrCl ≥50 mL/min based on Cockcroft-Gault formula (for patients in France, serum/plasma creatinine ≤1.5 × ULN or CrCl ≥60 mL/min based on Cockcroft-Gault formula). d. Albumin ≥30 g/L.
9. 9. Human immunodeficiency virus-infected patients who are healthy and have a low risk of acquired immunodeficiency syndrome-related outcomes are included in this trial.
10. 10. For patients who have partners who are pregnant or of childbearing potential: a condom is required along with a highly effective contraceptive method during the study and for 6 months after last study drug administration. Such methods deemed highly effective include a) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, b) progestogen-only hormonal contraception associated with inhibition of ovulation, c) intrauterine device (IUD), d) intrauterine hormone-releasing system (IUS), e) bilateral tubal occlusion, f) vasectomy, g) true sexual abstinence: when this is in line with the preferred and usual lifestyle of the subject [periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of abstinence].
11. 11. Willing to initiate ARAT therapy (either enzalutamide or abiraterone), prespecified by investigator, if randomized to Treatment Arm B.
12. 12. ECOG performance status 0 to 1.
13. 13. Willing and able to comply with all study requirements and treatments (including 177Lu-PNT2002) as well as the timing and nature of required assessments.
14. 14. Signed informed consent.

Exclusion criteria 22

1. 1. If noted in pathology report, prostate cancer with known significant (>10% present in cells) sarcomatoid or spindle cell components. Any small cell component in the cancer should result in exclusion.
2. 2. Prior treatment for prostate cancer ≤28 days prior to randomization, with the exclusion of first-line local external beam, ARAT, luteinizing hormone-releasing hormone agonist or antagonist therapy, or non-radioactive bone-targeted agents.
3. 3. Any prior cytotoxic chemotherapy for CRPC (e.g., cabazitaxel or docetaxel); chemotherapy for hormone-sensitive prostate cancer is allowed if the last dose was administered >1 year prior to consent.
4. 4. Prior treatment with systemic radionuclides (e.g. radium-223, rhenium-186, strontium-89).
5. 5. Prior immunotherapy, except for sipuleucel-T.
6. 6. Prior PSMA-targeted radioligand therapy, e.g., Lu-177-PSMA-617, I 131-1095.
7. 7. Prior poly ADP ribose polymerase inhibitor for prostate cancer.
8. 8. Patients who progressed on 2 or more lines of ARATs.
9. 9. Patients receiving bone-targeted therapy (e.g. denosumab, zoledronic acid) are excluded if they are not on stable doses for at least 4 weeks prior to randomization.
10. 10. Administration of an investigational agent ≤60 days or 5 half-lives, whichever is shorter, prior to randomization.
11. 11. Major surgery ≤30 days prior to randomization.
12. 12. Estimated life expectancy <6 months as assessed by the principal investigator.
13. 13. Presence of liver metastases >1 cm on abdominal imaging.
14. 14. A superscan on bone scan defined as a bone scan that demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint genitourinary tract activity.
15. 15. Dose escalation or initiation of opioids for cancer-related pain ≤30 days prior to consent up to and including randomization.
16. 16. Known presence of central nervous system metastases.
17. 17. Contraindications to the use of planned ARAT therapy, [Ga-68]-PSMA-11, [F-18]-DCFPyL or [Lu-177]-PNT2002 therapy, including but not limited to the following: a. Hypersensitivity to [Ga-68]-PSMA-11, [F-18]-DCFPyL or [Lu-177]-PNT2002 excipients (Diethylenetriaminepentaacetic acid (DTPA), Sodium ascorbate, L-ascorbic acid, Sodium gentisate, HCl, Sodium hydroxide) b. Recent myocardial infarction or arterial thrombotic events (in the past 6 months) or unstable angina (in the past 3 months), bradycardia or left ventricular ejection fraction measurement of < 50% c. History of seizures in patients planned to receive enzalutamide
18. 18. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer.
19. 19. Concurrent illness that may jeopardize the patient’s ability to undergo study procedures.
20. 20. Serious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedule. Patients that travel need to be capable of repeated visits even if they are on the control arm.
21. 21. Symptomatic cord compression or clinical or radiologic findings indicative of impending cord compression.
22. 22. Concurrent serious (as determined by the investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure unstable ischemia, uncontrolled symptomatic arrhythmia, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Radiological progression-free survival (rPFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG3) (bone) criteria.

Secondary endpoints 5

1. 1. ORR: proportion of patients with partial or complete response (PR or CR, respectively) by BICR based on RECIST 1.1 criteria (soft tissue) and PCWG3 criteria (bone). Duration of response: time from the first date of CR or PR by BICR to the first occurrence of PD by BICR based on PCWG3-modified RECIST 1.1 or death in the absence of progression.
2. 2. Overall survival (OS): time from randomization to date of death from any cause.
3. 3. Time from randomization to first symptomatic skeletal-related event.
4. 4. PSA response rate according to PCWG3 criteria (first occurrence of a 50% or more decline in PSA from baseline, confirmed by a second measurement at least 3 wk later). Biochemical PFS: time from randomization to the date of the first PSA increase from baseline ≥25% and ≥2 ng/mL above nadir confirmed by a 2nd PSA measurement defining progression ≥3 wk later per PCWG3.
5. 5. Safety Endpoints: • Frequency and severity of adverse events and serious adverse events using CTCAE v. 5.0. • Changes from baseline in physical exam findings, vital signs, clinical laboratory values, and electrocardiogram (ECG) values. • Number of patients discontinuing study drug due to adverse events.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Point Biopharma Inc.

Sponsor organisation

Point Biopharma Inc.

Address

4850 West 78th Street

City

Indianapolis

Postcode

46268-2385

Country

United States

Scientific contact point

Organisation

Point Biopharma Inc.

Contact name

Chief Medical Officer

Public contact point

Organisation

Point Biopharma Inc.

Contact name

Clinical Development Lead

Third parties 7

Locations

3 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications